Selective Antigen Specific dTβRII-expressing T cells

Selective Antigen Specific dTβRII-expressing T cells combined with B7-H3 CAR T cells

This protocol is designed as a phase I dose-escalation study. Procurement phase: During the procurement phase of this protocol, upon SABRE Procurement Consent and procurement eligibility confirmation, participants will undergo a non-mobilized apheresis for collection of mononuclear cells to be used for the CAR-TA T cell product manufacturing.

Treatment phase: Once the CAR-TA T cell products are released and patients are confirmed eligible for CAR-TA T cell product infusion, participants will undergo protocol therapy at participating site(s), consisting of a standard lymphodepleting chemotherapy preparative regimen with fludarabine and cyclophosphamide, followed by intravenous infusion of the combined CAR-TA T cell product.

This is a phase I dose-escalation study to determine the safety and feasibility of autologous CAR-TA T cells (B7-H3 CAR+ T cells administered with DNR-PRAME Tumor Antigen-specific T cells) following lymphodepleting chemotherapy in participants with relapsed/refractory rhabdomyosarcoma, Ewing sarcoma, neuroblastoma and Wilms tumor.

Patients will be enrolled to one of three planned dose levels with B7-H3 CAR T cell dose determined based on the percentage of B7-H3 transduced cells (B7-H3+ population of cells), and dTBRII-transduced PRAME TA-specific T cell dose based on the total cell population. Both doses will be based on the recipient's body weight and combined in a 1:1 ratio. The safety of the CAR-TA T cell product will be evaluated and the maximum tolerated dose (MTD) will be determined.

Live record on ClinicalTrials.gov →

• Diagnosis of relapsed/refractory rhabdomyosarcoma, Ewing sarcoma, neuroblastoma, or Wilms tumor
• Refractory disease, residual detectable disease or relapsed disease following available standard of care therapies with known clinical benefit for their specific tumor type, or unable to receive such therapies due to unacceptable toxicity or contraindication
• Measurable or evaluable disease by imaging, as determined following most recent therapy
• Age ≥ 1 year and < 24 years
• No systemic steroid exposure within 1 week of procurement

Inclusion criteria as written on the registry, trimmed. The full list, with exclusions, is on the live record.